Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trifunctional protein (TFP) plays a significant role in the mitochondrial beta-oxidation of long-chain fatty acids. Its deficiency impairs the energy generating function of this pathway and causes hypoketotic hypoglycemia once hepatic glycogen stores are depleted. A Reye-like syndrome, cardiomyopathy, and sudden death may follow. The diagnosis is based on demonstration of significantly decreased enzyme activity of at least two of the three involved enzymes in fibroblasts. The possibility of prospective diagnosis of TFP deficiency by newborn screening using tandem mass spectrometry (MS/MS) has not been evaluated. We report the postmortem diagnosis of a male newborn, who suffered sudden death at 2 wk of age, and his younger sister, who died of cardiomyopathy complicated by acute heart failure at the age of 6 mo, after she had acquired a common viral infection. Blood spots from the original newborn screening cards were the only remaining material from the patients. Analysis by MS/MS revealed acylcarnitine profiles consistent with either TFP or long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency. To prove the diagnosis, the alpha- and beta-subunit genes coding for TFP were examined. The patients were compound heterozygous for a 4-bp-deletion and an a-->g missense mutation, both in the same exon 3 donor consensus splice site. This is the first report of the diagnosis of TFP deficiency using blood spots obtained for newborn screening and suggests that TFP deficiency may be detectable by prospective newborn screening using MS/MS.
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PMID:Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. 1040 Jan 33

We describe a patient with carnitine-acylcarnitine translocase deficiency (MIM 212138), who presented with neonatal generalized seizures, heart failure, and coma. Laboratory evaluation revealed hypoglycemia, hyperammonemia, lactic acidemia, hyperuricemia, and mild dicarboxylic aciduria. The fact that total plasma carnitine (7.1 micromol/l [20-30]) and free carnitine (1.9 micromol/l [12-18]) were low together with a high acylcarnitine/free carnitine ratio of 2.7 [0.4-1.0] prompted acylcarnitine analysis. This revealed the presence of large amounts of long-chain derivatives including C(16:0), C(16:1), C(18:1), C(18:2). Based on these findings carnitine-acylcarnitine translocase deficiency was suspected which was confirmed by enzyme studies in fibroblasts. The underlying complex metabolic consequences of this defect are reviewed. Prenatal diagnosis was performed in a subsequent pregnancy and a defect ruled out by measurement of carnitine-acylcarnitine translocase activity in cultured chorionic villi cells. As the clinical recognition of a life-threatening fatty acid oxidation disorder may be difficult, defects in this pathway should be considered in any child with coma, an episode of a Reye-like syndrome, and cardiomyopathy. Since routine laboratory tests often do not provide clues about potential disorders and profiles of urinary organic acids may not be characteristic, we recommend to measure free carnitine and acylcarnitines in plasma in any child with hyperammonemia, hypo/hyperketotic hypoglycemia or lactic acidemia for prompt treatment, proper genetic counseling, and potential prenatal diagnosis.
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PMID:Carnitine-acylcarnitine translocase deficiency: metabolic consequences of an impaired mitochondrial carnitine cycle. 1087 4

Carnitine deficiency syndrome is a rare and potentially fatal but treatable metabolic disorder. I present a 6-year-old girl with primary systemic carnitine deficiency (SCD) proved by very low plasma carnitine level. Her major clinical features included neonatal metabolic acidosis, epilepsy, recurrent infections, acute encephalopathy, and dilated cardiomyopathy with heart failure before 4 years of age. Other features such as hepatomegaly, hypoglycemia, or hyperammonemia were noted around 5 years of age. Her health improved with resolving cardiomyopathy after the use of L-carnitine (50-100 mg/kg/day). Patients with SCD have high morbidity and mortality. If SCD is suggested as a cause of Reye-like syndrome or dilated cardiomyopathy, L-carnitine therapy should be initiated as a diagnostic test immediately, until the definite diagnosis is confirmed.
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PMID:Primary systemic carnitine deficiency presenting as recurrent Reye-like syndrome and dilated cardiomyopathy. 1263 40